This invention relates to pipette means, more especially, but not exclusively, of an at least partially automated kind, having the object of improving the consistency of sampling and dispensing volume, and of dilution ratio, by eliminating a measure of human error from these operations.
The traditional form of pipette in which a sample is aspirated by lung power and expelled by the same means, or by gravity, can be accurate for sample quantities of the order of as little as 5 milliliter. Many projects, for example in connection with analysis of biological fluids, require the moving of hundreds or thousands of samples usually of the order of 5 microliter, and often also their dilution. Some degree of automation is necessary on grounds of time, accuracy and consistency; and apparatus exists which can automatically aspirate and dispense with high accuracy and consistency. However, such apparatus has usually been expensive, including, for example, precision syringes for sample measurement. The present invention permits at least as good accuracy and consistency to be achieved, using components which are cheap and even, in some instances, expendable.
According to the invention pipette means has aspirating and expelling means and a substantially cylindrical tube connected to a pipette tip for fluid flow therebetween; the expelling means being arranged to apply pressure to the outer surface of the cylindrical tube, the diameter and wall thickness of which being chosen so that said tube is compressed elastically and substantially uniformly and circumferentially to reduce the internal volume thereof, tending to expel any liquid from the pipette tip; and the aspirating means being arranged to relieve pressure from the outer surface of said tube allowing the tube to expand substantially circumferentially and uniformly so that liquid may thereby be drawn into the pipette tip.
The expelling and aspirating means may operate by the application and relief respectively of fluid pressure to and from the cylindrical tube.
In one embodiment of the invention the pipette means is arranged for sampling, diluting and dispensing, and has diluent valve means which permit a controlled amount of liquid diluent to pass through the cylindrical tube to the pipette tip to diluent a sample when the expelling means applies pressure to the cylindrical tube.
The diluting means may include a diluent syringe, diluent valve means and syringe operating means; arranged so that when the cylindrical tube aspirates a sample into the pipette tip the syringe draws diluent from a reservoir; and after reaching the end of its stroke the syringe drives its charge of diluent through the cylindrical tube and out of the pipette tip.
The syringe operating means may be a piston and cylinder combination, the stroke of the piston being longer than the stroke of the syringe, and the excess stroke of the piston being adapted to operate the diluent valve means at the end of each stroke of the syringe.
Another form of syringe operating means includes an electric motor driving a lead screw connected to the syringe plunger, arranged so that at each end of the stroke of the syringe relative rotary movement between the body of the electric motor and the lead screw operates the diluent valve means.
In the pipette means, the aspirating and expelling means may include, for operation thereof, valve means and fluid pressure control means, the valve means being adapted to apply pressure to and release pressure from the cylindrical tube, the pressure being supplied, in use, from an external source of fluid pressure.
As an alternative to reliance on an external source of fluid pressure, the pipette means may be adapted for the inclusion of a source of fluid pressure which may be a miniature gas storage cylinder of carbon dioxide.
It may be arranged that the source of fluid pressure for the pipette means is also the source of diluent, which may for that purpose be a pressurised reservoir.
In another arrangement, the source of diluent is a head tank arranged, in use, at a level above the cylindrical tube, which level provides pressure adequately to compress said cylindrical tube.
Desirably the head tank is provided with liquid levelling means for keeping the liquid level therein substantially constant. Such means may be, for example, spring means supporting the head tank, said spring means being so proportioned that as liquid is withdrawn from the tank the spring means, experiencing a smaller force, raises the tank so that the liquid level therein is kept constant above a predetermined datum.
In the pipette means, any valve means may include a valve of the electrical solenoid operated kind; and may further include timing means arranged to control the sequence and timing of operation of any such valve.
In another embodiment the pipette means has valve means and a reservoir, the valve means being arranged so that in a first position thereof pressure is removed from the cylindrical tube to aspirate a sample into the pipette tip and the reservoir is charged with fluid pressure from a source thereof, and in another position pressure is applied to the cylindrical tube to compress it, and the reservoir is discharged through the cylindrical tube, at least to assist in expelling the sample from the pipette tip.
In a further embodiment, the diluent may be stored in a pressurised reservoir, and the quantity delivered through the cylindrical tube controlled by a timer and solenoid operated valve.
The cylindrical tube may be made of latex rubber. If low absorption of water by the tube is specially desirable, the cylindrical tube may be latex rubber, lined with a thin layer of silicone rubber. A further possibility is to make the cylindrical tube of a mixture of silicone rubber and natural rubber.
Desirably, exhausting of fluid from around the cylindrical tube is controlled in rate, eg by an adjustable needle valve. If required, the temperature of the pipette means, and of fluids supplied to it, may be controlled thermostatically. As an alternative to fluid pressure, compression and expansion of the cylindrical tube may be by alternately tightening and releasing a coaxial helical filament.
What has been referred to in the foregoing as a "cylindrical tube" is also referred to in the specification as a "squashed tube"; although in the working of the invention the tube is not squashed, in the usual meaning of the word, that is to say the tube is not flattened in use, but retains its circular cross section.